Complex-linear invariants of biochemical networks

The nonlinearities found in molecular networks usually prevent mathematical analysis of network behaviour, which has largely been studied by numerical simulation. This can lead to difficult problems of parameter determination. However, molecular networks give rise, through mass-action kinetics, to polynomial dynamical systems, whose steady states are zeros of a set of polynomial equations. These equations may be analysed by algebraic methods, in which parameters are treated as symbolic expressions whose numerical values do not have to be known in advance. For instance, an "invariant" of a network is a polynomial expression on selected state variables that vanishes in any steady state. Invariants have been found that encode key network properties and that discriminate between different network structures. Although invariants may be calculated by computational algebraic methods, such as Gr\"obner bases, these become computationally infeasible for biologically realistic networks. Here, we exploit Chemical Reaction Network Theory (CRNT) to develop an efficient procedure for calculating invariants that are linear combinations of "complexes", or the monomials coming from mass action. We show how this procedure can be used in proving earlier results of Horn and Jackson and of Shinar and Feinberg for networks of deficiency at most one. We then apply our method to enzyme bifunctionality, including the bacterial EnvZ/OmpR osmolarity regulator and the mammalian 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase glycolytic regulator, whose networks have deficiencies up to four. We show that bifunctionality leads to different forms of concentration control that are robust to changes in initial conditions or total amounts. Finally, we outline a systematic procedure for using complex-linear invariants to analyse molecular networks of any deficiency.Comment: 36 pages, 6 figure

Trace Spaces: an Efficient New Technique for State-Space Reduction

State-space reduction techniques, used primarily in model-checkers, all rely on the idea that some actions are independent, hence could be taken in any (respective) order while put in parallel, without changing the semantics. It is thus not necessary to consider all execution paths in the interleaving semantics of a concurrent program, but rather some equivalence classes. The purpose of this paper is to describe a new algorithm to compute such equivalence classes, and a representative per class, which is based on ideas originating in algebraic topology. We introduce a geometric semantics of concurrent languages, where programs are interpreted as directed topological spaces, and study its properties in order to devise an algorithm for computing dihomotopy classes of execution paths. In particular, our algorithm is able to compute a control-flow graph for concurrent programs, possibly containing loops, which is "as reduced as possible" in the sense that it generates traces modulo equivalence. A preliminary implementation was achieved, showing promising results towards efficient methods to analyze concurrent programs, with very promising results compared to partial-order reduction techniques

Malaria and land use: a spatial and temporal risk analysis in Southern Sri Lanka

Malaria / Waterborne diseases / Disease vectors / Land use / Water use / GIS / Statistical analysis / Risks / Mapping / Public health / Sri Lanka / Uda Walawe / Thanamalvila / Embilipitiya

The effect of spacer morphology on the aerosolization performance of metered-dose inhalers

Purpose: Respiratory drug delivery has been attracted great interest for the past decades, because of the high incidence of pulmonary diseases. However, despite its invaluable benefits, there are some major drawbacks in respiratory drug delivery, mainly due to the relatively high drug deposition in undesirable regions. One way to improve the efficiency of respiratory drug delivery through metered-dose inhalers (MDI) is placing a respiratory spacer between the inhaler exit and the mouth. The aim of this study was to assess the effect of type and shape of spacer on the aerosolization performance of MDIs. Methods: A commercial Beclomethasone Dipropionate (BDP) MDI alone or equipped with two different spacer devices (roller and pear type) widely distributed in the world pharmaceutical market was used. The effect of spacers was evaluated by calculating aerosolization indexes such as fine particle fraction (FPF), mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) using the next generation impactor. Results: Although one of the spacers resulted in superior outcomes than the other one, but it was not statistically significant. Conclusion: The results confirmed that the type and shape of spacer did not substantially influence the aerosolization performance of MDIs

Simulation Study of an LWFA-based Electron Injector for AWAKE Run 2

The AWAKE experiment aims to demonstrate preservation of injected electron beam quality during acceleration in proton-driven plasma waves. The short bunch duration required to correctly load the wakefield is challenging to meet with the current electron injector system, given the space available to the beamline. An LWFA readily provides short-duration electron beams with sufficient charge from a compact design, and provides a scalable option for future electron acceleration experiments at AWAKE. Simulations of a shock-front injected LWFA demonstrate a 43 TW laser system would be sufficient to produce the required charge over a range of energies beyond 100 MeV. LWFA beams typically have high peak current and large divergence on exiting their native plasmas, and optimisation of bunch parameters before injection into the proton-driven wakefields is required. Compact beam transport solutions are discussed.Comment: Paper submitted to NIMA proceedings for the 3rd European Advanced Accelerator Concepts Workshop. 4 pages, 3 figures, 1 table Changes after revision: Figure 2: figures 2 and 3 of the previous version collated with plots of longitudinal electric field Line 45: E_0 = 96 GV/m Lines 147- 159: evaluation of beam loading made more accurate Lines 107 - 124: discussion of simulation geometry move

Geometric Path Integrals. A Language for Multiscale Biology and Systems Robustness

In this paper we suggest that, under suitable conditions, supervised learning can provide the basis to formulate at the microscopic level quantitative questions on the phenotype structure of multicellular organisms. The problem of explaining the robustness of the phenotype structure is rephrased as a real geometrical problem on a fixed domain. We further suggest a generalization of path integrals that reduces the problem of deciding whether a given molecular network can generate specific phenotypes to a numerical property of a robustness function with complex output, for which we give heuristic justification. Finally, we use our formalism to interpret a pointedly quantitative developmental biology problem on the allowed number of pairs of legs in centipedes

Innovative prefabricated modular structures – an Overview and life cycle energy analysis

Speed of construction and improved environmental performance are two critical concerns which modern construction industry pays a significant amount of attention on. Employing innovative prefabricated modular structures is one key strategy used to achieve these goals. However, there is an absence of detailed scientific research or case studies dealing with the potential environmental benefits of prefabrication, particularly in the areas of embodied energy savings resulting from waste reduction and improved efficiency of material usage. This paper gives a brief overview of prefabricated modular structures and aims to quantify the embodied energy of modular prefabricated steel and timber multi-residential buildings in order to determine whether this form of construction provides improved environmental performance over conventional concrete construction methods. A case study was carried out on an eight-storey, 3943 m2 multi-residential building. It was found that a steel-structured prefabricated system resulted in a significantly reduced material consumption of up to 78% by mass compared to conventional concrete construction. However, the prefabricated steel building resulted in an increase (~50%) in embodied energy compared to the concrete building. This form of construction has the potential to contribute significantly towards improved environmental sustainability in the construction industry

Filling in the gaps: a road map to establish a model system to study developmental programmed cell death

Only a handful of model systems for studying programmed cell death (PCD) exist. The model Arabidopsis thaliana has generated a plethora of knowledge, but it is essential to introduce new models to broaden our understanding of the commonalities of PCD. This review focuses on Aponogeton madagascariensis (the lace plant) as a choice model to study PCD in vivo. PCD plays a key role in plant development and defence. Thus, identifying key regulators across plants is a priority in the field. The formation of perforations in lace plant leaves in areas called areoles is a striking example of PCD. Cells undergoing PCD within areoles can be easily identified from a loss of their anthocyanin pigmentation. In contrast, cells adjacent to veins, non-PCD cells, retain anthocyanins, creating a gradient of cell death. The spatiotemporal pattern of perforation formation, a gradient of cell death within areoles, and the availability of axenic cultures provide an excellent in vivo system to study mechanisms of developmental PCD. The priorities to further develop this model involve sequencing the genome, establishing transformation protocols, and identifying anthocyanin species to determine their medicinal properties. We discuss practical methodologies and challenges associated with developing the lace plant as a model to study PCD

Multiple Perspectives on Implementing Inter-University Computer Conferencing

The purpose of this symposium is to discuss the organization, design, implementation and preliminary evaluation of an inter-university collaborative learning experience that used computer mediated communication (CMC) to link graduate students in several universities to discuss issues related to distance education. The discussion is based on the Globaled project, a computer conference that was set up and implemented for the second time, during the Fall 1993 semester. Globaled was first implemented during the Spring of 1992. With the increasing offering of distance education as a graduate discipline in many traditional universities, Globaled, can be seen as a unique way to connect graduate students across States and countries to participate in discussions related to the field of distance education